Meloxicam for the treatment of respiratory diseases in pigs

ABSTRACT

A method of treating or preventing a respiratory disease in a pig is described that includes administering to the pig in need thereof an effective amount of meloxicam or a pharmaceutically acceptable salt thereof.

BACKGROUND OF THE INVENTION 1. Technical Field

The invention relates to the use of meloxicam or a pharmaceuticallyacceptable salt thereof for preparing a pharmaceutical composition forthe treatment or prevention of respiratory diseases in pigs.

2. Background Information

Respiratory disease in pigs belongs to the most important healthproblems in swine production. Porcine respiratory disease is primarilycaused by infectious agents, but environmental factors have a stronginfluence. The relevant pathogens include mycoplasmas, bacteria, andviruses (e.g., G. Christensen, V. Sorensen, and J. Mousing, Diseases ofthe Respiratory System, In: Diseases of Swine, B. E. Straw, S.D'Allaire, W. L. Mengeling, & D. J. Taylor (eds), Iowa State UniversityPress, Ames, Iowa (1999) pp. 913-940).

The most important measures for the control of porcine respiratorydisease are to improve herd management and housing conditions andintroduce a vaccination program. However, if pigs have developedrespiratory disease, they have to be treated.

Current therapy of porcine respiratory disease includes treatment withantibiotics. The successful use of various types of antibiotics isdescribed, including β-lactams, quinolones, and tetracyclines (e.g., I.Lang, M. Rose, E. Thomas, & E. Zschiesche, A Field Study of Cefquinomefor the Treatment of Pigs with Respiratory Disease, Revue Med Vet 8-9,(2002) pp. 575-580).

It is known that cyclooxygenase-2 (COX-2) plays a relevant role in thepathophysiology of porcine pleuropneumonia caused by Actinobacilluspleuropneumoniae. Isolated porcine alveolar macrophages increase theirCOX-2 activity after exposure to Actinobacillus pleuropneumoniae (W. S.Cho & C. Chae, In vitro Effects of Actinobacillus pleuropneumoniae onInducible Nitric Oxide Synthase and Cyclooxygenase-2 in Porcine AlveolarMacrophages, Am J Vet Res 64, (2003) pp. 1514-1518). Moreover, in situhybridization (W. S. Cho & C. Chae, Expression of Cyclooxygenase-2 inSwine Naturally Infected with Actinobacillus pleuropneumoniae, VetPathol 40, (2003) pp. 25-31) and immunohistochemistry (W. S. Cho & C.Chae, Immunohistochemical Detection of Cyclooxygenase-2 in Lungs of PigsNaturally Infected with Actinobacillus pleuropneumoniae, J Comp Pathol127, (2002) pp. 274-279) showed increased COX-2 expression in lungs ofpigs naturally infected with Actinobacillus pleuropneumoniae.

Moreover, it is well-known that acetylsalicylic acid (aspirin) can beused for the treatment of pigs with respiratory disease. However, littleinformation on controlled clinical studies is available: for a review,see A. Laval, Utilisation des Anti-inflammatoires chez le Porc, Rec MédVét 168 (8/9) (1992) pp. 733-744. Ketoprofen, and, to a lesser extent,flunixin decrease fever induced by experimental infection withActinobacillus pleuropneumoniae (J. M. Swinkels, A. Pijpers, J. C.Vernooy, A. Van Nes, & J. H. Verheijden, Effects of Ketoprofen andFlunixin in Pigs Experimentally Infected with Actinobacilluspleuropneumoniae, J Vet Pharmacol Ther 17, (1994) pp. 299-303). However,no effects on lung lesions were observed. Ketoprofen was further testedin a controlled, blinded clinical field study (M. F. De Jong, O.Sampimon, J. P. Arnaud, G. Theunissen, G. Groenland, & P. J. Werf, AClinical Study with a Non Steroid Antiinflammatory Drug, 14, (1996) 659IPVS). In this study, ketoprofen had no effect on clinical score,relapse, or cure rate.

Indomethacin alleviated experimental endotoxin-induced respiratoryfailure in pigs (N. C. Olson, T. T. Brown, J. R. Anderson, & D. L.Anderson, Dexamethasone and Indomethacin Modify Endotoxin-InducedRespiratory Failure in Pigs, J Appl Physiol 58, (1985) pp. 274-284).

Meloxicam is a non-steroidal anti-inflammatory compound that belongs tothe oxicam class and exerts potent anti-inflammatory, anti-exudative,and anti-pyretic activity. The efficacy of meloxicam as an adjunctivetherapy in the treatment of respiratory infections in cattle has beenwidely proven. Recently meloxicam was approved for the treatment of MMA(A. Hirsch et al., J Vet Pharmacol Therap 26 (2003) pp. 355-360) andlocomotor disorders in pigs (G. Friton et al., Berl Münch TierärztlWschr 116 (2003) pp. 421-426).

A review article (P. Lees, The Pharmacokinetics of Drugs Used in theTreatment of Respiratory Diseases in Cattle and Pigs, (1991) pp. 67-74,Hatfield, U.K. Proc. Royal Vet. Coll.) focuses on pharmacokinetics usedin the treatment of respiratory disease in cattle and pigs; however,non-steroidal anti-inflammatory drugs data for pigs was almost entirelylacking and only lists data for cattle including meloxicam.

The use of meloxicam in conjunction with antibiotics in bovinerespiratory disease is well-established (H. Schmidt, H. Philipp, E.Salomon, & K. Okkinga, Effekte der zusäitzlichen Gabe von Metacam(Meloxicam) auf den Krankheitsverlauf bei Rindern mitAtemwegserkrankungen, Der praktische Tierarzt 81 (2000) pp. 240-244) andregistered in the EU. However, to date no information on the use ofmeloxicam in pigs with respiratory disease is publicly available.

Since the pharmacokinetics in pigs and cattle differ substantially formeloxicam (plasma half-time in cattle is 26 hours whereas it is 2.5hours in pigs), there is no expectation that the successful use ofmeloxicam in cattle should also be beneficial for pigs. Moreover, thecausative agents for bovine and porcine respiratory disease differsubstantially.

The problem underlying the present invention was to provide a medicationfor the prevention or treatment of respiratory diseases in pigs, one ofthe most important health problems in swine production.

BRIEF DESCRIPTION OF THE INVENTION

It has been found surprisingly that meloxicam can be used for thetreatment or prevention of respiratory diseases in pigs.

Accordingly, the invention relates to the use of meloxicam or apharmaceutically acceptable salt thereof for preparing a pharmaceuticalcomposition for the treatment or prevention of respiratory diseases inpigs.

Moreover, the invention relates to a method of treating or preventingrespiratory diseases in pigs, which method comprises administering aneffective amount of meloxicam to the pigs in need thereof.

Furthermore, the invention relates to veterinary preparation containingmeloxicam as well as at least one antibiotic selected from the groupconsisting of β-lactams, quinolones, tetracyclines, sulfonamides,fenicoles, and macrolides.

Another aspect of the invention is a ready-to-use two-component systemfor the treatment of respiratory diseases in pigs, wherein:

-   -   (a) one component contains meloxicam and a pharmaceutically        acceptable carrier; and    -   (b) the other component contains at least one antibiotic        selected from the group consisting of β-lactams, quinolones,        tetracyclines, sulfonamides, fenicoles, and macrolides and a        pharmaceutically acceptable carrier.

Still another aspect of the invention is an article of manufacturecomprising packaging material contained within which is a compositionconsisting of meloxicam and a pharmaceutically acceptable carrier, and alabel which indicates that the composition can be used to treat orprevent respiratory diseases in pigs.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the incidence of fever (rectal temperature ≥40.56° C.) inpercent following the first treatment in a group of pigs treated withoxytetracycline and meloxicam (♦), in a group of pigs treated withoxytetracycline alone (o), and in the untreated control (Δ).

FIG. 2 shows the efficacy of meloxicam in drinking water in reducinglung lesions caused by experimental Swine Influenza Virus (SIV)infection on study days 7 and 14.

DETAILED DESCRIPTION OF THE INVENTION

Preferably the invention relates to the use of meloxicam or apharmaceutically acceptable salt thereof for preparing a pharmaceuticalcomposition in a form suitable for systemic or oral administration forthe treatment or prevention of respiratory diseases in pigs. Meloxicam(4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide)of formula

is an active substance which belongs to the group of NSAIDs(non-steroidal-anti-inflammatory drugs). Meloxicam and the sodium andmeglumine salt thereof (N-methyl-D-glucamine salt) are described inEP-A-0 002 482 (corresponding to U.S. Pat. No. 4,233,299), each of whichis hereby incorporated by reference.

Meloxicam may be used according to the invention in the form of aphysiologically acceptable acid addition salt. By physiologicallyacceptable acid addition salts are meant, according to the invention,the meglumine, sodium, potassium, or ammonium salt, preferably themeloxicam meglumine salt.

In a further preferred embodiment, the pharmaceutical composition isadministered corresponding to a daily dose of meloxicam ranging from0.01 mg/kg to 5.0 mg/kg, preferably from 0.1 mg/kg to 3.5 mg/kg, inparticular from 0.2 mg/kg to 2.0 mg/kg.

The pharmaceutical composition is preferably administered in a formsuitable for injection, in particular for intramuscular injection, or inform of water soluble granules for administration via drinking water oras top dressing on feed.

A suitable injection formulation is disclosed, for example, in Example25 of EP-A-0 002 482. Furthermore, such injection solutions mayadditionally contain excipients selected from among citric acid,lecithin, gluconic acid, tartaric acid, phosphoric acid and EDTA or thesalts thereof as disclosed in the Examples 1 to 5 of the InternationalPatent Application WO 01/97813 (corresponding to U.S. Patent App. PubNo. 2002/0035107), each of which is hereby incorporated by reference.Moreover, an injection solution of meloxicam for needleless injectionsis disclosed in the International Patent Application WO 03/049733(corresponding to U.S. Patent App. Pub No. 2003/0119825), each of whichis hereby incorporated by reference.

Suitable water soluble granules for administration via drinking water oras top dressing on feed are, for example, disclosed in the InternationalPatent Application PCT/EP03/11802 (corresponding to U.S. Patent App. PubNo. 2004/0234596), each of which is hereby incorporated by reference.

In a preferred embodiment of the invention, the meloxicam granulescontain a binder which may be selected from amonghydroxypropylmethylcellulose, polyvinylpyrrolidone, gelatine, starch,and polyethylene glycol ether, preferably hydroxypropylmethylcellulose,polyvinylpyrrolidone, and polyethylene glycol ether, and most preferablyhydroxypropylmethylcellulose and polyvinylpyrrolidone.

In another preferred embodiment of the invention, meloxicam granulescontain a sweetener, which may be selected from among sodium saccharine,aspartame, and SUNETT® (acesulfame K), preferably sodium saccharine oraspartame.

Particularly preferred according to the invention are meloxicam granulescontaining a flavoring agent which may be selected from among vanilla,honey flavoring, apple flavoring, and contramarum, preferably honeyflavoring and apple flavoring.

Also particularly preferred are meloxicam granules in which the carrieris selected from among lactose, glucose, mannitol, xylitol, sucrose, andsorbitol, preferably glucose, lactose, or sorbitol, more preferablyglucose or lactose, and most preferably glucose.

Most preferred are the following granules of meloxicam recipes:

Example A: 0.6% Meloxicam Granules

g/100 g Meloxicam 0.6 Meglumine 0.42 Hydroxypropylmethylcellulose 3.00Povidone 2.00 Glucose monohydrate 93.98

Example B: 1.2% Meloxicam Granules

g/100 g Meloxicam 1.2 Meglumine 0.84 Hydroxypropylmethylcellulose 3.00Collidone 25 2.0 Glucose Monohydrate 92.96

Example C: 0.6% Meloxicam Granules

g/100 g Meloxicam 0.6 Meglumine 0.42 Pharmacoat 606 4.0 Macrogol 60001.0 Acesulfame K 0.3 Lactose 93.68

Example D: 0.6% Meloxicam Granules

g/100 g Meloxicam 0.6 Meglumine 0.42 Pharmacoat 606 4.75 Macrogol 60000.25 Acesulfame K 0.3 Liquid vanilla flavoring 0.05 Lactose 93.63

Particularly preferred are meloxicam granules in which the content ofmeloxicam is between 0.05% and 4%, preferably between 0.1% and 2%,preferably between 0.3% and 1.8%, more preferably between 0.4% and 1.5%,and most preferably 1.2%. Also particularly preferred are meloxicamgranules which contain meglumine and meloxicam in a molar ratio of about9:8 to 12:8, preferably 10:8.

Meloxicam can be used according to the invention to treat or preventrespiratory diseases in any breed of swines. Preferably pigs selectedfrom the swine breeds American Landrace, American Yorkshire, AngelnSaddleback, Arapawa Island, Ba Xuyen, Bantu, Bazna, Beijing Black,Belarus Black Pied, Belgian Landrace, Bentheim Black Pied, Berkshire,Black Slavonian, British Landrace, British Lop, Bulgarian White,Cantonese, Chester White, Czech Improved White, Danish Landrace,Dermantsi Pied, Duroc, Dutch Landrace, Fengjing, Finnish Landrace,French Landrace, German Landrace, Gloucestershire Old Spots, Guinea Hog,Hampshire, Hereford, Hezuo, Iberian, Italian Landrace, Jinhua, Kele,Krskopolje, Kunekune, Lacombe, Large Black, Large Black-white, LargeWhite, Lithuanian Native, Mangalitsa, Meishan, Middle White, Minzhu,Mong Cai, Mukota, Mora Romagnola, Moura, Mulefoot, Neijiang, Ningxiang,Norwegian Landrace, Ossabaw Island, Oxford Sandy and Black, PhilippineNative, Pietrain, Poland China, Red Wattle, Saddleback, Spots,Swabian-Hall, Swedish Landrace, Tamworth, Thuoc Nhieu, Tibetan,Turopolje, Vietnamese Potbelly, Welsh, and Wuzhishan, in particularAmerican Landrace, Belgian Landrace, British Landrace, Danish Landrace,Dutch Landrace Finnish Landrace, French Landrace, German Landrace,Italian Landrace, and Pietrain can be treated with meloxicam accordingto the present invention.

Furthermore preferred is the administration of meloxicam is inconjunction with an antibiotic, preferably selected from the groupconsisting of β-lactams, quinolones, tetracyclines, sulfonamides,fenicoles, and macrolides. Most preferred are amoxicillin,oxytetracycline, florfenicol, tylosin, tilmicosin, and sulfamethazine.

The dose of antibiotic is not critical per se and depends strongly onthe different efficacies of the antibiotics used. As a rule up to 150.0mg/kg, preferably from 0.1 mg/kg to 120 mg/kg, in particular from 10mg/kg to 110 mg/kg of an antibiotic are co-administered together withmeloxicam.

The following dose ranges are most preferred:

Amoxicillin: 5 mg/kg to 30 mg/kg, in particular about 10 mg/kg;Oxytetracycline: 20 mg/kg to 70 mg/kg, in particular about 30 mg/kg;Florfenicol: 10 mg/kg to 20 mg/kg, in particular about 15 mg/kg;Tylosin: 10 mg/kg to 25 mg/kg, in particular about 16 mg/kg;Tilmicosin: 5 mg/kg to 30 mg/kg, in particular 10 mg/kg to 20 mg/kg; andSulfamethazine: 80 mg/kg to 150 mg/kg, in particular about 100 mg/kg.

The phrase “co-administration” (or “administration in conjunctionwith”), in defining use of meloxicam and an antibiotic, is intended toembrace administration of each agent in a sequential manner in a regimenthat will provide beneficial effects, in particular, reduction of thesymptoms of the respiratory disease in the affected pig of the drugcombination. The phrase also is intended to embrace co-administration ofthese agents in a substantially simultaneous manner, such as in a singlecapsule or injection solution having a fixed ratio of these activeagents or in multiple, separate capsules for each agent.

Accordingly, meloxicam and the antibiotic may be co-administered in acombined form, or separately or separately and sequentially wherein thesequential administration is preferably close in time.

Preferably the medicament according to this invention is used for theprevention or treatment of Porcine Respiratory Disease Complex ingrowing or fattening pigs; or for the prevention or treatment ofrespiratory diseases in pigs caused by mycoplasmas, in particularMycoplasma hyopneumoniae, Mycoplasma hyorhinis, for the prevention ortreatment of respiratory diseases in pigs caused by bacteria inparticular Actinobacillus spp., in particular Actinobacilluspleuropneumoniae, Bordetella bronchiseptica, Pasteurella multocida,Arcanobacterium pyogenes, Streptococcus spp., and Staphylococcus spp.,or for the prevention or treatment of respiratory diseases in pigscaused by viruses, in particular Swine Influenza Virus, Aujetzky'sVirus, Porcine Reproductive and Respiratory Syndrome Virus, PorcineCircovirus, and Transmissible Gastroenteritis and Porcine RespiratoryCoronavirus.

Most preferably the medicament according to this invention is used forthe prevention or treatment of respiratory diseases in pigs caused byMycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae, Bordetellabronchiseptica, Pasteurella multocida, Streptococcus suis, SwineInfluenza Virus, and Porcine Reproductive and Respiratory SyndromeVirus.

The Examples that follow serve to illustrate the use of meloxicamaccording to the invention. They are intended solely as possibleprocedures described by way of example, without restricting theinvention to their content.

Example 1: Efficacy of Meloxicam in Pigs with ExperimentalActinobacillus Pleuropneumoniae Infection

The study was a controlled, randomized, and blinded exploratory studyunder experimental conditions with a parallel group design.

Crossbred pigs of about 10 weeks of age were challenged with a singleintranasal inoculation of Actinobacillus pleuropneumoniae. The next day,pigs were included in the study and treated if they fulfilled thefollowing inclusion criteria: rectal temperature ≥40° C. and clinicalsymptoms of acute or subacute infectious respiratory disease.

Twenty-four (12 castrated male and 12 female) pigs were included andrandomly allocated to three treatment groups with 8 pigs per group. Thetreatment groups were:

Group Treatment 1 untreated 2 oxytetracycline 3 oxytetracycline andmeloxicam

Meloxicam was administered as 0.5% solution, at 0.5 mg/kg daily on threeconsecutive days, oxytetracycline as 20% long-acting solution (OXYTET®200) at 20 mg/kg as single injection.

Relevant criteria for the evaluation of efficacy were incidence offever, clinical parameters of respiratory disease, deaths, and lunglesions at necropsy 10 days after first treatment or after spontaneousdeath. The percentage of affected lung tissue was calculated by lobe andaveraged for the total lung.

Challenge with Actinobacillus pleuropneumoniae lead to severepleuropneumonia within 12 hours.

The incidence of fever (rectal temperature ≥40.56° C.) following thefirst treatment was lower in group 3 (♦) than in groups 1 (Δ), and 2 (o)(cp. FIG. 1).

The best treatment response in clinical parameters was observed in group3.

The number of pigs which died during the three days following firsttreatment is displayed below.

Group (n = 8 per group) Deaths 1 7 2 1 3 0

The mean extent of lung lesions was less severe in group 3 than in theother groups (see below).

Group Lung lesions (%) 1 60 2 35 3 14

Meloxicam in addition to antibiotic treatment effectively reduced fever,clinical symptoms of respiratory disease, deaths, and the extent of lunglesions in pigs with experimental Actinobacilluspleuropneumoniae-infection.

Example 2: Efficacy of Meloxicam in Drinking Water in Experimental SwineInfluenza Virus Infection

The aim of this study was to test the efficacy of meloxicam granulesdissolved in drinking water in pigs experimentally infected with SwineInfluenza Virus (SIV).

The study was an open, negative controlled randomized laboratory studycarried out according to GCP at one site.

Meloxicam granules containing 6 mg meloxicam per gram were offered tothe pigs in the treatment groups (A+B) via drinking water in aconcentration of 1 g granules per liter drinking water ad libitum for 7consecutive days. This resulted in an actual meloxicam uptake of 0.8 mgper kg body weight per day. The pigs in the control group (C) receivedmunicipal drinking water ad libitum.

30 pigs were infected with SIV on study day 0. 10 pigs were allocated toeach of the three groups A, B, and C. Treatment (groups A and B) startedafter SIV challenge on the same day.

The study animals were clinically examined daily on study days 0 to 7and 14. They were weighed on study days 7 and 14. All animals of group Aand 5 animals of group C were euthanized and necropsied on study day 7;the remaining study animals, group B and 5 study animals of group C, onstudy day 14.

It is the major finding of this study that meloxicam granulesadministered continuously in the drinking water at an approximate dailydose of 0.8 mg/kg body weight significantly alleviated the developmentof lung lesions caused by experimental infection with SIV during thefirst week after challenge. FIG. 2 shows the quantity of lung lesions bylung lobe on study days 7 and 14.

On study day 7 the percentage of lung tissue affected with SIV-relatedlesions (median value) was 8.9% in meloxicam group A and 23.8% in thecontrol group (5 study animals of group C).

Moreover, meloxicam-treated pigs reached significantly higher weightgains during the two weeks following infection than untreated controls.Mean daily weight gain in the interval study day 0 to 7 was 557 g inmeloxicam group A and 257 g in the control (5 study animals of group C).In the interval study day 0 to 14, mean daily weight gain was 629 g inmeloxicam group B and 486 g in the control (5 study animals of group C).

The area under the curve of the clinical index score (CIS), a sum of therelevant clinical parameters, over study days 0 to 7 was significantlysmaller in groups A and B than in group C.

Thus oral treatment with meloxicam granules at a dose of 0.8 mgmeloxicam per kg body weight per day for 7 consecutive was anefficacious treatment for SIV infection.

Example 3: Field Trial Regarding the Effect of Meloxicam in the PorcineRespiratory Disease Complex (PRDC) in Growing/Fattening Pigs Materialsand Methods

A medium scale farm (560 sows) with a previous history of recurring PRDCepisodes was selected. A double-blinded randomized study was carried outwith the selection of 162 growing animals with a mean age of 90 days atthe onset of PRDC clinical signs. Animals were randomly allocated to 8pens and divided into two treatment groups, with respect to equal sexratio, same housing and feeding conditions and genetic background. Group1 (PC) received 800 ppm chlorotetracycline in the feed over 8consecutive days plus a single IM injection of a placebo (isotonicsaline) at d0 (start of the trial, n=82). Group 2 (M) received 800 ppmchlorotetracycline in the feed over 8 consecutive days plus a single IMinjection of 0.4 mg/kg bodyweight meloxicam (METACAM® 2%, BoehringerIngelheim GmbH) at d0 (n=80). Clinical parameters were assessed as thedaily Respiratory Score (RS), using a 3 point score (0=absence of signsto 3=abdominal breathing and disordered general condition) over 8consecutive days and the total number of additional required injectablemedications (AIM). Growth performance data for each group included theAverage Daily Gain (ADG) for the following trial periods: d90 to d117,d117 to d170 (slaughtering), and d90 to d170 of age. Mortality was alsocalculated for these time periods. Slaughterhouse records per group,included the percentage of each lung surface (LS) affected by chronicand acute respiratory lesions.

Student's t-Test and Pearson's Chi-Square Test were used for theconsequent comparisons of means and frequencies between trial groups.

Results and Discussion

RS and AIM in the meloxicam group were significantly lower (p<0.05)compared to the control group. Same applies for LS affected by acutelesions (p<0.01), while no differences were observed for LS in chroniccases (Table 1).

TABLE 1 RS, LS: Mean (SD); AIM number (%) Treatment Group PC MSignificance RS  0.70 (0.63)^(a) 0.50 (0.51)^(b) p = 0.0289 AIM (%)10/82 (12.2%)^(a) 2/80 (2.5%)^(b) x² = 4.226 LS(chronic)  5.96(2.28)^(a) 5.91 (2.32)^(a) p = 0.893 LS (acute)  3.71 (1.81)^(a) 2.64(2.03)^(b) p = 0.0007 ^(a,b)Values in a row with different superscriptsdiffer significantly

The analysis of growth performance data revealed significant differencesbetween groups at d90 to d117 (p<0.05, Table 2).

TABLE 2 ADG: Mean (SD) Trial Period Group d90 to d117 d117 to d170 d90to d170 PC 0.64 (0.09)^(a) 0.89 (0.06)^(a) 0.81 (0.03)^(a) M 0.67(0.10)^(b) 0.89 (0.06)^(a) 0.82 (0.03)^(a) ^(a,b)Values in a column withdifferent superscripts differ significantly (p < 0.05)

TABLE 3 Mortality: Number of animals/group (%) Trial Period Group d90 tod117 d117 to d170 d90 to d170 PC 6/82 (7.32%)^(a) 1/76 (1.22%) 7/82(8.54%) M 0/80 (0.00%)^(b) 1/80 (1.25%) 1/80 (1.25%) ^(a,b)Values in acolumn with different superscripts differ significantly (p < 0.05)

Under the conditions of this study, the reduction of the prevalence ofrespiratory signs as well as the reduced overall number of requiredinjectable antibiotic medications are indicative for the potentanti-inflammatory activity of meloxicam. The latter could become avaluable adjunctive measure, especially when respiratory distress isassociated with remarkable reduction of the feed intake. The initialdifferences in growth performance and in mortality rate could beexplained by the fact that meloxicam, when combined with properantimicrobial medication, contributes to faster recovery from arespiratory inflammation and faster restoring of the distorted growthrate of affected animals. Further research on the evaluation of feedintake and the use of meloxicam in PRDC recurring episodes is required.

1. A method of treating or preventing a respiratory disease caused by avirus in a pig, the method comprising administering to a pig sufferingfrom a respiratory disease an effective amount of meloxicam or apharmaceutically acceptable salt thereof.
 2. The method of claim 1,wherein the disease is caused by Swine Influenza Virus, Aujetzky'sVirus, Porcine Reproductive and Respiratory Syndrome Virus, PorcineCircovirus, or Transmissible Gastroenteritis and Porcine RespiratoryCoronavirus.
 3. The method of claim 1, wherein the disease is PorcineRespiratory Disease Complex and the pig is a growing or fattening pig.4. The method of claim 1, wherein the meloxicam or a pharmaceuticallyacceptable salt thereof is administered systemically or orally.
 5. Themethod of claim 1, wherein the meloxicam or a pharmaceuticallyacceptable salt thereof is administered by injection.
 6. The method ofclaim 1, wherein the meloxicam or a pharmaceutically acceptable saltthereof is administered in a daily dose ranging from 0.01 mg/kg to 5.0mg/kg.
 7. The method of claim 1, wherein the meloxicam or apharmaceutically acceptable salt thereof is administered via drinkingwater or as top dressing on feed in soluble granules.
 8. The method ofclaim 1, further comprising: administering an antibiotic to the pig,wherein the antibiotic is selected from the group consisting ofβ-lactams, quinolones, tetracyclines, sulfonamides, fenicoles,macrolides, and any one or more combinations thereof.
 9. The method ofclaim 8, wherein the antibiotic is oxytetracycline orchlorotetracycline.
 10. The method of claim 8, wherein the antibiotic isadministered in conjunction with the meloxicam or a pharmaceuticallyacceptable salt thereof.
 11. The method of claim 1, wherein meloxicam isadministered in the form of granules, wherein the granules furthercomprise: meglumine; a carrier selected from the group consisting oflactose, glucose, mannitol, xylitol, sucrose, and sorbitol; and a binderselected from the group consisting of hydroxypropylmethylcellulose,polyvinylpyrrolidone, gelatine, starch, and polyethylene glycol ether.